Gas-phase ion mobility of protonated aldehydes in helium measured using a selected ion flow-drift tube.

RATIONALE: In soft chemical ionization mass spectrometry, analyte ions are produced via ion-molecule reactions in the reactor. When an electric field E is imposed, the ion drift velocity vd determines the reaction time and the effective ion temperature. Agreement between experimental ion mobilities and theoretical predictions confirms the accuracy of the ion residence time measurement procedure. METHODS: A selected ion flow-drift tube (SIFDT), an instrument with a chemical ionization source, was used to produce protonated aldehydes and selectively inject them into the resistive glass drift tube filled with He. Arrival-time distributions of ions were obtained using the Hadamard modulation. Reduced ion mobilities were then obtained at a pressure of 2 hPa in the E/N range of 5-15 Td. Theoretical ion mobility values were calculated using two methods: hard-sphere approximation and trajectory modelling. RESULTS: The measured mobilities of three saturated and three unsaturated protonated aldehydes do not show substantial variation across the studied E/N range. Effective temperatures calculated using the Wannier formula from measured gas temperatures ranged from 300 to 315 K. Experimentally obtained values of the near-zero- E/N-reduced ion mobilities agree with both methods of calculations typically within ±3% standard deviation (maximum ±5%). CONCLUSIONS: The experimental SIFDT values of reduced mobilities in He of protonated aldehyde molecules generated from a chemical ionization source are in close agreement with two different theoretical methods based on the density functional theory calculations of ion geometries and partial atomic charges. Besides its fundamental importance, the ion mobility results validate the correct operation of the drift tube reactor and the ion residence time measurement procedure. Diffusion losses can also be determined from these results.

Combining Thermal Desorption with Selected Ion Flow Tube Mass Spectrometry for Analyses of Breath Volatile Organic Compounds.

An instrument integrating thermal desorption (TD) to selected ion flow tube mass spectrometry (SIFT-MS) is presented, and its application to analyze volatile organic compounds (VOCs) in human breath is demonstrated for the first time. The rationale behind this development is the need to analyze breath samples in large-scale multicenter clinical projects involving thousands of patients recruited in different hospitals. Following adapted guidelines for validating analytical techniques, we developed and validated a targeted analytical method for 21 compounds of diverse chemical class, chosen for their clinical and biological relevance. Validation has been carried out by two independent laboratories, using calibration standards and real breath samples from healthy volunteers. The merging of SIFT-MS and TD integrates the rapid analytical capabilities of SIFT-MS with the capacity to collect breath samples across multiple hospitals. Thanks to these features, the novel instrument has the potential to be easily employed in clinical practice.

Gas phase H+, H3O+ and NH4+ affinities of oxygen-bearing volatile organic compounds; DFT calculations for soft chemical ionisation mass spectrometry.

Quantum chemistry calculations were performed using the density functional theory, DFT, to understand the structures and energetics of organic ions relevant to gas phase ion chemistry in soft chemical ionisation mass spectrometry analytical methods. Geometries of a range of neutral volatile organic compound molecules and ions resulting from protonation, the addition of H3O+ and the addition of NH4+ were optimised using the B3LYP hybrid DFT method. Then, the total energies and the normal mode vibrational frequencies were determined, and the total enthalpies of the neutral molecules and ions were calculated for the standard temperature and pressure. The calculations were performed for several feasible structures of each of the ions. The proton affinities of several benchmark molecules agree with the accepted values within ±4 kJ mol-1, indicating that B3LYP/6-311++G(d,p) provides chemical accuracy for oxygen-containing volatile organic compounds. It was also found that the binding energies of H3O+ and NH4+ to molecules correlate with their proton affinities. The results contribute to the understanding of ligand switching ion-molecule reactions important for secondary electrospray ionisation, SESI, and selected ion flow tube, SIFT, mass spectrometries.

Robust Automated SIFT-MS Quantitation of Volatile Compounds in Air Using a Multicomponent Gas Standard.

Selected ion flow tube mass spectrometry, SIFT-MS, has been widely used in industry and research since its introduction in the mid-1990s. Previously described quantitation methods have been advanced to include a gas standard for a more robust and repeatable analytical performance. The details of this approach to calculate the concentrations from ion-molecule reaction kinetics based on reaction times and instrument calibration functions determined from known concentrations in the standard mix are discussed. Important practical issues such as the overlap of product ions are outlined, and best-practice approaches are presented to enable them to be addressed during method development. This review provides a fundamental basis for a plethora of studies in broad application areas that are possible with SIFT-MS instruments.

Accurate selected ion flow tube mass spectrometry quantification of ethylene oxide contamination in the presence of acetaldehyde.

In September 2020, traces of ethylene oxide (a toxic substance used as a pesticide in developing countries but banned for use on food items within the European Union) were found in foodstuffs containing ingredients derived from imported sesame seed products. Vast numbers of foodstuffs were recalled across Europe due to this contamination, leading to expensive market losses and extensive trace exposure of ethylene oxide to consumers. Therefore, a rapid analysis method is needed to ensure food safety by high-throughput screening for ethylene oxide contamination. Selected ion flow tube mass spectrometry (SIFT-MS) is a suitable method for rapid quantification of trace amounts of vapours in the headspace of food samples. It turns out, however, that the presence of acetaldehyde complicates SIFT-MS analyses of its isomer ethylene oxide. It was proposed that a combination of the H3O+ and NO+ reagent ions can be used to analyse ethylene oxide in the presence of acetaldehyde. This method is, however, not robust because of the product ion overlaps and potential interferences from other matrix species. Thus, we studied the kinetics of the reactions of the H3O+, NO+, OH- and O-˙ ions with these two compounds and obtained their rate coefficients and product ion branching ratios. Interpretation of these experimental data revealed that the OH- anions are the most suitable SIFT-MS reagents because the product ions of their reactions with acetaldehyde (CH2CHO- at m/z 43) and ethylene oxide (C2H3O2- at m/z 59) do not overlap.

How to Use Ion-Molecule Reaction Data Previously Obtained in Helium at 300 K in the New Generation of Selected Ion Flow Tube Mass Spectrometry Instruments Operating in Nitrogen at 393 K.

Selected ion flow tube mass spectrometry (SIFT-MS) instruments have significantly developed since this technique was introduced more than 20 years ago. Most studies of the ion-molecule reaction kinetics that are essential for accurate analyses of trace gases and vapors in air and breath were conducted in He carrier gas at 300 K, while the new SIFT-MS instruments (optimized to quantify concentrations down to parts per trillion by volume) operate with N2 carrier gas at 393 K. Thus, we pose the question of how to reuse the data from the extensive body of previous literature using He at room temperature in the new instruments operating with N2 carrier gas at elevated temperatures. Experimentally, we found the product ions to be qualitatively similar, although there were differences in the branching ratios, and some reaction rate coefficients were lower in the heated N2 carrier gas. The differences in the reaction kinetics may be attributed to temperature, an electric field in the current flow tubes, and the change from He to N2 carrier gas. These results highlight the importance of adopting an updated reaction kinetics library that accounts for the new instruments' specific conditions. In conclusion, almost all previous rate coefficients may be used after adjustment for higher temperatures, while some product ion branching ratios need to be updated.

A SIFT-MS study of positive and negative ion chemistry of the ortho-, meta- and para-isomers of cymene, cresol, and ethylphenol.

Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) is a soft ionisation technique based on gas phase ion-molecule reaction kinetics for the quantification of trace amounts of volatile organic compound vapours. One of its previous limitations is difficulty in resolving isomers, although this can now be overcome using different reactivities of several available reagent cations and anions (H3O+, NO+, O2+˙, O-˙, OH-, O2-˙, NO2-, NO3-). Thus, the ion-molecule reactions of these eight ions with all isomers of the aromatic compounds cymene, cresol and ethylphenol were studied to explore the possibility of their immediate identification and quantification without chromatographic separation. Rate coefficients and product ion branching ratios determined experimentally for the 72 reactions are reported. DFT calculations of their energetics confirmed the feasibility of the suggested reaction pathways. All positive ion reactions proceeded fast but largely did not discriminate between the isomers. The reactivity of the anions was much more varied. In all cases, OH- reacts by proton transfer forming (M-H); NO2- and NO3- were unreactive. The differences observed for product ion branching ratios can be used to identify isomers approximately.

Recent developments and applications of selected ion flow tube mass spectrometry (SIFT-MS).

Selected ion flow tube mass spectrometry (SIFT-MS) is now recognized as the most versatile analytical technique for the identification and quantification of trace gases down to the parts-per-trillion by volume, pptv, range. This statement is supported by the wide reach of its applications, from real-time analysis, obviating sample collection of very humid exhaled breath, to its adoption in industrial scenarios for air quality monitoring. This review touches on the recent extensions to the underpinning ion chemistry kinetics library and the alternative challenge of using nitrogen carrier gas instead of helium. The addition of reagent anions in the Voice200 series of SIFT-MS instruments has enhanced the analytical capability, thus allowing analyses of volatile trace compounds in humid air that cannot be analyzed using reagent cations alone, as clarified by outlining the anion chemistry involved. Case studies are reviewed of breath analysis and bacterial culture volatile organic compound (VOC), emissions, environmental applications such as air, water, and soil analysis, workplace safety such as transport container fumigants, airborne contamination in semiconductor fabrication, food flavor and spoilage, drugs contamination and VOC emissions from packaging to demonstrate the stated qualities and uniqueness of the new generation SIFT-MS instrumentation. Finally, some advancements that can be made to improve the analytical capability and reach of SIFT-MS are mentioned.

Different reactivities of H3 O+ (H2 O)n with unsaturated and saturated aldehydes: ligand-switching reactions govern the quantitative analytical sensitivity of SESI-MS.

RATIONALE: The detection sensitivity of secondary electrospray ionisation mass spectrometry (SESI-MS) is much lower for saturated aldehydes than for unsaturated aldehydes. This needs to be understood in terms of gas phase ion-molecule reaction kinetics and energetics to make SESI-MS analytically more quantitative. METHODS: Parallel SESI-MS and selected ion flow tube mass spectrometry (SIFT-MS) analyses were carried out of air containing variable accurately determined concentrations of saturated (C5, pentanal; C7, heptanal; C8 octanal) and unsaturated (C5, 2-pentenal; C7, 2-heptenal; C8, 2-octenal) aldehyde vapours. The influence of the source gas humidity and the ion transfer capillary temperature, 250 and 300°C, in a commercial SESI-MS instrument was explored. Separate experiments were carried out using SIFT to determine the rate coefficients, k73 , for the ligand-switching reactions of the H3 O+ (H2 O)3 ions with the six aldehydes. RESULTS: The relative slopes of the plots of SESI-MS ion signal against SIFT-MS concentration were interpreted as the relative SESI-MS sensitivities for these six compounds. The sensitivities for the unsaturated aldehydes were 20 to 60 times greater than for the corresponding C5, C7 and C8 saturated aldehydes. Additionally, the SIFT experiments revealed that the measured k73 are three or four times greater for the unsaturated than for the saturated aldehydes. CONCLUSIONS: The trends in SESI-MS sensitivities are rationally explained by differences in the rates of the ligand-switching reactions, which are justified by theoretically calculated equilibrium rate constants derived from thermochemical density functional theory (DFT) calculations of Gibb's free energy changes. The humidity of SESI gas thus favours the reverse reactions of the saturated aldehyde analyte ions, effectively suppressing their signals in contrast to their unsaturated counterparts.

The Human Skin Volatolome: A Systematic Review of Untargeted Mass Spectrometry Analysis.

The analysis of volatile organic compounds (VOCs) can provide important clinical information (entirely non-invasively); however, the exact extent to which VOCs from human skin can be signatures of health and disease is unknown. This systematic review summarises the published literature concerning the methodology, application, and volatile profiles of skin VOC studies. An online literature search was conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis, to identify human skin VOC studies using untargeted mass spectrometry (MS) methods. The principal outcome was chemically verified VOCs detected from the skin. Each VOC was cross-referenced using the CAS number against the Human Metabolome and KEGG databases to evaluate biological origins. A total of 29 studies identified 822 skin VOCs from 935 participants. Skin VOCs were commonly sampled from the hand (n = 9) or forearm (n = 7) using an absorbent patch (n = 15) with analysis by gas chromatography MS (n = 23). Twenty-two studies profiled the skin VOCs of healthy subjects, demonstrating a volatolome consisting of aldehydes (18%), carboxylic acids (12%), alkanes (12%), fatty alcohols (9%), ketones (7%), benzenes and derivatives (6%), alkenes (2%), and menthane monoterpenoids (2%). Of the VOCs identified, 13% had putative endogenous origins, 46% had tentative exogenous origins, and 40% were metabolites from mixed metabolic pathways. This review has comprehensively profiled the human skin volatolome, demonstrating the presence of a distinct VOC signature of healthy skin, which can be used as a reference for future researchers seeking to unlock the clinical potential of skin volatolomics. As significant proportions of identified VOCs have putative exogenous origins, strategies to minimise their presence through methodological refinements and identifying confounding compounds are discussed.

Selected Ion Flow Tube Mass Spectrometry as a Tool to Understand Hydride Atomization and the Fate of Free Analyte Atoms in an Externally Heated Quartz Tube Atomizer.

Hydride atomization and the fate of free analyte atoms in an externally heated quartz tube atomizer (QTA) were investigated employing selected ion flow tube mass spectrometry (SIFT-MS). SIFT-MS proved to be ideally suited to study water concentration in gases leaving the atomizer. This made it possible to quantify the oxygen "contaminant" flow rate to QTA as 0.04-0.05 mL min-1. This is valid for typical conditions of hydride generation. Most significantly, studies of temperature influence on water concentration resulted in detailed insight into hydrogen radical-forming reactions between oxygen and hydrogen. Minimum QTA temperatures required to generate hydrogen radicals under a variety of different flow rates and compositions of the QTA atmosphere were found to be in the range between 585 and 800 °C. The ability of SIFT-MS to detect extremely low concentrations of arsane and selane was employed to quantify the fraction of As and Se removed from the QTA in the form of hydride in dependence on QTA temperature under typical conditions of hydride generation. It was found that free As atoms formed by atomization of arsane decay to different species than to arsane. In the case of selane under typical atomization conditions, the efficiency of the decay of free Se atoms to selane was between 50 and 100% in dependence on actual flow rates and compositions of the QTA atmosphere.

Kinetics of reactions of NH4 + with some biogenic organic molecules and monoterpenes in helium and nitrogen carrier gases: A potential reagent ion for selected ion flow tube mass spectrometry.

RATIONALE: To assess the suitability of NH4 + as a reagent ion for trace gas analysis by selected ion flow tube mass spectrometry, SIFT-MS, its ion chemistry must be understood. Thus, rate coefficients and product ions for its reactions with typical biogenic molecules and monoterpenes need to be experimentally determined in both helium, He, and nitrogen, N2 , carrier gases. METHODS: NH4 + and H3 O+ were generated in a microwave gas discharge through an NH3 and H2 O vapour mixture and, after m/z selection, injected into He and N2 carrier gas. Using the conventional SIFT method, NH4 + reactions were then studied with M, the biogenic molecules acetone, 1-propanol, 2-butenal, trans-2-heptenal, heptanal, 2-heptanone, 2,3-heptanedione and 15 monoterpene isomers to obtain rate coefficients, k, and product ion branching ratios. Polarisabilities and dipole moments of the reactant molecules and the enthalpy changes in proton transfer reactions were calculated using density functional theory. RESULTS: The k values for the reactions of the biogenic molecules were invariably faster in N2 than in He but similar in both bath gases for the monoterpenes. Adducts NH4 + M were the dominant product ions in He and N2 for the biogenic molecules, whereas both MH+ and NH4 + M product ions were observed in the monoterpene reactions; the monoterpene ratio correlating (R2  = 0.7) with the proton affinity, PA, of the monoterpene molecule as calculated. The data indicate that this adduct ion formation is the result of bimolecular rather than termolecular association. CONCLUSIONS: NH4 + can be a useful reagent ion for SIFT-MS analyses of molecules with PA(M) < PA(NH3 ) when the dominant single product ion is the adduct NH4 + M. For molecules with PA(M) > PA(NH3 ), such as monoterpenes, both MH+ and NH4 + M ions are likely products, which must be determined along with k by experiment.

Atomization of As and Se volatile species in a dielectric barrier discharge atomizer after hydride generation: Fate of analyte studied by selected ion flow tube mass spectrometry.

Atomization of hydrides and their methylated analogues in a dielectric barrier discharge (DBD) plasma atomizer was investigated. Selected ion flow tube mass spectrometry (SIFT-MS) was chosen as a detector being capable of selective detection of non-atomized original volatile species allowing thus direct quantification of atomization efficiency. Selenium hydride (SeH2) and three volatile arsenic species, namely arsenic hydride (AsH3), monomethylarsane (CH3AsH2) and dimethylarsane ((CH3)2AsH), were selected as model analytes. The mechanistic study performed contributes to understanding of the atomization processes in atomic absorption spectrometry (AAS). The presented results are compatible with a complete atomization of arsenic hydride as well as its methylated analogues and with atomization efficiency of SeH2 below 80%. Using AsH3 as a model analyte and a combination of AAS and SIFT-MS detectors has revealed that the hydride is not atomized, but decomposed in the DBD atomizer in absence of hydrogen fraction in the carrier gas. Apart from investigation of analyte atomization, the SIFT-MS detector is capable of quantitative determination of water vapor content being either transported to, or produced in the atomizer. This information is crucial especially in the case of the low-power/temperature DBD atomizer since its performance is sensitive to the amount of water vapor introduced into the plasma.

Ternary association reactions of H3 O+ , NO+ and O2 +• with N2 , O2 , CO2 and H2 O; implications for selected ion flow tube mass spectrometry analyses of air and breath.

RATIONALE: The reactions of the reagent ions used for trace gas analysis in selected ion flow tube mass spectrometry (SIFT-MS), R+ , viz. H3 O+ , NO+ and O2 + , with the major gases in air and breath samples, M, viz. N2 , O2 , CO2 and H2 O, are investigated. These reactions are seen to form weakly-bound adduct ions, R+ M, by ternary association reactions that must not be mistaken for genuine volatile organic compound (VOC) analyte ions. METHODS: The ternary association rate coefficients mediated by helium (He) carrier gas atoms, k3a , have been determined for all combinations of R+ and M, which form R+ M adduct ions ranging in m/z from 47 (H3 O+ N2 ) to 76 (O2 +• CO2 ). This was achieved by adding variable amounts of M (up to 0.5 mbar pressure) into the He carrier gas (pressure of 1.33 mbar) in a SIFT-MS flow tube at 300 K. Parabolic curvature was observed on some of the semi-logarithmic decay curves that allowed the rate coefficients mediated by M molecules, k3b , to be estimated. RESULTS: Values of k3a were found to range from 1 × 10-31  cm6  s-1 to 5 × 10-29  cm6  s-1 , which form mass spectral R+ M "ghost peaks" of significant strength when analysing VOCs at parts-per-billion concentrations. It was seen that the R+ M adduct ions (except when M is H2 O) react with H2 O molecules by ligand switching forming the readily recognised monohydrates of the initial reagent cations R+ H2 O. Whilst this ligand switching diminishes the R+ M adduct ghost peaks, it does not eliminate them entirely. CONCLUSIONS: The significance of these adduct ions for trace gas analysis by SIFT-MS in the low m/z region is alluded to, and some examples are given of m/z spectral overlaps of the R+ M and R+ H2 O adduct cations with analyte cations of VOCs formed by analysis of complex media like exhaled breath, warning that ghost peaks will be enhanced using nitrogen carrier gas in SIFT-MS.

Sensitivity of secondary electrospray ionization mass spectrometry to a range of volatile organic compounds: Ligand switching ion chemistry and the influence of Zspray™ guiding electric fields.

RATIONALE: Secondary electrospray ionization (SESI) is currently only semi-quantitative. In the Zspray™ arrangement of SESI-MS, the transfer of ions from near atmospheric pressure to a triple quadrupole is achieved by guiding electric fields that partially desolvate both reagent and analyte ions which must be understood. Also, to make SESI-MS more quantitative, the mechanisms and the kinetics of the reaction processes, especially ligand switching reactions of hydrated hydronium reagent ions, H3 O+ (H2 O)n , with volatile organic compound (VOC) molecules, need to be understood. METHODS: A modified Zspray™ ESI ion source operating at sub-atmospheric pressure with analyte sample gas introduced via an inlet coaxial with the spray was used. Variation of the ion-guiding electric fields was used to reveal the degree of desolvation of both reagent and analyte ions. The instrument sensitivity was determined for several classes of VOCs by introducing bag samples of suitably varying concentrations as quantified on-line using selected ion flow tube MS. RESULTS: Electric field desolvation resulted in largely protonated VOCs, MH+ , and their monohydrates, MH+ H2 O, and for some VOCs proton-bound dimer ions, MH+ M, were formed. There was a highly linear response of the ion signal to the measured VOC sample concentration, which provided the instrument sensitivities, S, for 25 VOCs. The startling results show very wide variations in S from near 0 to 1 for hydrocarbons, and up to 100, on a relative scale, for polar compounds such as monoketones and unsaturated aldehydes. CONCLUSIONS: The complex ion chemistry occurring in the SESI ion source, largely involving gas-phase ligand switching, results in widely variable sensitivities for different classes of VOCs. The sensitivity is observed to depend on the dipole moment and proton affinity of the analyte VOC molecule, M, and to decrease with the observed fraction of MH+ H2 O, but other yet unrecognized factors must play a significant role.

Ligand Switching Ion Chemistry: An SIFDT Case Study of the Primary and Secondary Reactions of Protonated Acetic Acid Hydrates with Acetone.

A study was performed of the reactions of protonated acetic acid hydrates, CH3COOHH+(H2O)n, with acetone molecules, CH3COCH3, using a selected ion flow-drift tube (SIFDT). The rationale for this study is that hydrated protonated organic molecules are major product ions in secondary electrospray ionization mass spectrometry (SESI-MS) and ion mobility spectrometry (IMS). Yet the formation and reactivity of these hydrates are only poorly understood, and kinetics data are only sparse. The existing SIFDT instrument in our laboratory was upgraded to include an octupole ion guide and a separate drift tube by which hydrated protonated ions can be selectively injected into the drift tube reactor and their reactions with molecules studied under controlled conditions. This case study shows that, in these hydrated ion reactions with acetone molecules, the dominant reaction process is ligand switching producing mostly proton-bound dimer ions (CH3COCH3)H+(CH3COOH), with minor branching into (CH3COCH3)H+(H2O). This switching reaction was observed to proceed at the collisional rate, while other studied hydrated ions reacted more slowly. An attempt is made to understand the reaction mechanisms and the structures of the reaction intermediate ions at the molecular level. Secondary switching reactions of the asymmetric proton-bound dimer ions lead to a formation of strongly bound symmetrical dimers (CH3COCH3)2H+, the terminating ion in this ion chemistry. These results strongly suggest that, in SESI-MS and IMS, the presence of a polar compound, like acetone in exhaled breath, can suppress the analyte ions of low concentration compounds like acetic acid thus compromising their quantification.

Selected ion flow tube mass spectrometry for targeted analysis of volatile organic compounds in human breath.

The analysis of volatile organic compounds (VOCs) within breath for noninvasive disease detection and monitoring is an emergent research field that has the potential to reshape current clinical practice. However, adoption of breath testing has been limited by a lack of standardization. This protocol provides a comprehensive workflow for online and offline breath analysis using selected ion flow tube mass spectrometry (SIFT-MS). Following the suggested protocol, 50 human breath samples can be analyzed and interpreted in <3 h. Key advantages of SIFT-MS are exploited, including the acquisition of real-time results and direct compound quantification without need for calibration curves. The protocol includes details of methods developed for targeted analysis of disease-specific VOCs, specifically short-chain fatty acids, aldehydes, phenols, alcohols and alkanes. A procedure to make custom breath collection bags is also described. This standardized protocol for VOC analysis using SIFT-MS is intended to provide a basis for wider application and the use of breath analysis in clinical studies.

Cross Platform Analysis of Volatile Organic Compounds Using Selected Ion Flow Tube and Proton-Transfer-Reaction Mass Spectrometry.

Volatile breath metabolites serve as potential disease biomarkers. Online mass spectrometry (MS) presents real-time quantification of breath volatile organic compounds (VOCs). The study aims to assess the relationship between two online analytical mass spectrometry techniques in the quantification of target breath metabolites: selected ion flow tube mass spectrometry (SIFT-MS) and proton-transfer-reaction time-of-flight mass spectrometry (PTR-ToF-MS). The two following techniques were employed: (i) direct injection with bag sampling using SIFT-MS and PTR-ToF-MS and (ii) direct injection and thermal desorption (TD) tube comparison using PTR-ToF-MS. The concentration of abundant breath metabolites, acetone and isoprene, demonstrated a strong positive linear correlation between both mass spectrometry techniques (r = 0.97, r = 0.89, respectively; p < 0.001) and between direct injection and TD tube (r = 0.97, r = 0.92, respectively; p < 0.001) breath sampling techniques. This was reflected for the majority of short chain fatty acids and alcohols tested (r > 0.80, p < 0.001). Analyte concentrations were notably higher with the direct injection of a sampling bag compared to the TD method. All metabolites produced a high degree of agreement in the detection range of VOCs between SIFT-MS and PTR-ToF-MS, with the majority of compounds falling within 95% of the limits of agreement with Bland-Altman analysis. The cross platform analysis of exhaled breath demonstrates strong positive correlation coefficients, linear regression, and agreement in target metabolite detection rates between both breath sampling techniques. The study demonstrates the transferability of using data outputs between SIFT-MS and PTR-ToF-MS. It supports the implementation of a TD platform in multi-site studies for breath biomarker research in order to facilitate sample transport between clinics and the laboratory.

Reagent and analyte ion hydrates in secondary electrospray ionization mass spectrometry (SESI-MS), their equilibrium distributions and dehydration in an ion transfer capillary: Modelling and experiments.

RATIONALE: Secondary electrospray ionization (SESI) in a water spray environment at atmospheric pressure involves the reactions of hydrated hydronium reagent ions, H3 O+ (H2 O)n , with trace analyte compounds in air samples. Understanding the formation and dehydration of reagent and analyte ions is the foundation for meaningful quantification of trace compounds by SESI-mass spectrometry (MS). METHODS: A numerical model based on gas-phase ion thermochemistry is developed that describes equilibria in H3 O+ (H2 O)n reagent cluster ion distributions and ligand switching reactions with polar NH3 molecules leading to equilibrated hydrated ammonium ions NH4 + (H2 O)m . The model predictions are compared with experimental results obtained using a cylindrical SESI source coupled to an ion-trap mass spectrometer via a heated ion transfer capillary. Non-polar isoprene, C5 H8 , was used to further probe the nature of the reagent ions. RESULTS: Equilibrium distributions of H3 O+ (H2 O)n ions and their reactions with NH3 molecules have been characterized by the model in the near-atmospheric pressure SESI source. NH3 analyte molecules displace H2 O ligands from the H3 O+ (H2 O)n ions at the collisional rate forming NH4 + (H2 O)m ions, which travel through the heated ion transfer capillary losing H2 O molecules. The data for variable NH3 concentrations match the model predictions and the C5 H8 test substantiates the notion of dehydration in the heated capillary. CONCLUSIONS: Large cluster ions formed in the SESI region are dehydrated to H3 O+ (H2 O)1,2,3 and NH4 + (H2 O)1,2 while passing through the heated capillary, and considerable diffusion losses also occur. This phenomenon is also predicted for other polar analyte molecules, A, that can undergo similar switching reactions, thus forming AH+ and AH+ (H2 O)m analyte ions.